Regulation of thrombin-induced plasminogen activator inhibitor-1 in 4T1 murine breast cancer cells
Regulation of thrombin-induced plasminogen activator inhibitor-1 in 4T1 murine breast cancer cells
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DOI：
10.1097/mbc.0b013e3283497647
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发表时间：
2011-10-01
影响因子：
1.1
通讯作者：
Mackman, Nigel
中科院分区：
文献类型：
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作者：
McEachron, Troy A.;Church, Frank C.;Mackman, Nigel
蛋白酶激活受体-1 （PAR-1）和PAR-2在癌细胞中过度表达，这些受体的激活有助于恶性肿瘤的发生。我们最近发现凝血酶激活PAR-1，从而诱导PAR-2的转激活，导致4T1小鼠乳腺腺癌细胞中纤溶酶原激活物抑制剂-1 （PAI-1）的表达增加。我们的目的是分析调节凝血素诱导的PAI-1表达的信号转导途径。我们发现凝血酶刺激激活了4T1细胞中的ERK1/2-ELK1-EGR1通路。此外，p42/p44 MAPK信号的抑制降低了PAI-1的表达。这些结果开始描述凝血酶激活PAR-1/PAR-2复合物诱导4T1小鼠乳腺癌细胞系PAI-1表达的机制。血液凝固纤维蛋白溶解：576-582 (C) 2011 Wolters Kluwer Health垂直bar Lippincott Williams & Wilkins。
Protease-activated receptor-1 (PAR-1) and PAR-2 are overexpressed in cancer cells and activation of these receptors contributes to malignancy. We have recently shown that thrombin activates PAR-1, which induces transactivation of PAR-2, resulting in increased plasminogen activator inhibitor-1 (PAI-1) expression in 4T1 murine mammary adenocarcinoma cells. Our goal was to analyze the signal transduction pathways that regulate thrombin-induced PAI-1 expression. We found that thrombin stimulation activates the ERK1/2-ELK1-EGR1 pathway in 4T1 cells. Furthermore, inhibition of p42/p44 MAPK signaling reduced PAI-1 expression. These results begin to delineate the mechanism by which thrombin activates a PAR-1/PAR-2 complex to induce PAI-1 expression in the 4T1 murine breast cancer cell line. Blood Coagul Fibrinolysis 22:576-582 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.